This is the second revision of a competing renewal of a project which now focuses upon the origin and mechanism behind the recurrent 11;22 translocation in humans. This is the only recurrent, non-Robertsonian constitutional translocation in humans which gives rise to the supernumerary der(22)t(11;22) syndrome. Also, such 11;22 translocations have also been implicated in Ewing's sarcoma and, perhaps, in other tumors as well. Five specific aims are now proposed. The first will be to isolate and characterize, including sequencing, the 11;22 breakpoint of the der(22) and der(11) of a translocation carrier. The second aim will be to examine at a molecular level the breakpoints of other t(11;22) families and examine the aggregated breakpoint sequences for specific motifs or sequence patterns. The third aim will be to examine the 22q11.23 breakpoint sequence cluster, identified in 11;22 translocations, with other translocations involving this specific location of chromosome 22. The fourth aim will address the origin of the apparent 3:1 meiotic segregation seen in unbalanced offspring, where adjacent I segregation would be expected. The various mechanisms will be tested by marker segregation in t(11;22) families. The final aim will be to examine the physical location and arrangement of chromosomes 11 and 22 in both meiosis and mitosis to gain additional clues toward the reason for this recurrent form of rearrangement.